In June 2001, investigators reported the exciting discovery of a newly recognized human paramyxovirus that may explain a significant portion of acute respiratory illnesses. Relatively little is known regarding the epidemiology of this human metapneumovirus (HMPV). The few published studies have exclusively involved patients from outside of the United States. Available data suggest that HMPV may cause as much as 15% of acute respiratory illness, may cause serious respiratory illness and death, that HMPV has at least two major genotypes, and that it infects all age-groups. There remain many questions regarding HMPV infections. Are specific populations, such as the elderly or the immunocompromised, at increased risk of infection? Are rural populations are greater risk of HMPV infection. Are specific HMPV genotypes more often associated with severe disease? Are there significant temporal, geographical, or genetic variations in HMPV disease? We plan to initiate a series of epidemiological studies of human metapneumovirus with a long term goal of reducing HMPV morbidity. This application is our first step towards that goal. In it we will identify Midwestern populations with a high prevalence of HMPV infection and determine if US Midwestern HMPV isolates genotypically differ from those collected outside of the United States. We will accomplish this by using RT-PCR to evaluate1500 viral culture specimens collected during the years 2000 to 2004 from outpatients and inpatients suffering from acute respiratory infection at a Midwestern regional medical center. Through univariate and multivariate techniques, demographic and clinical risk factors for HMPV RT-PCR positivity will be identified among the 1500 patients studied. Specimens that are RT-PCR positive will be cultured and HMPV isolates will be phylogenetically compared with previously identified HMPV isolates for genetic variation. These data will facilitate the development of more comprehensive epidemiological studies, and guide future intervention studies in reducing HMPV morbidity.